We had previously determined amino acid sequences of human, mouse, rat, and bovine retinal S-antigen (SAg) and rat pineal gland SAg. Immunogenic sites and four uveitopathogenic sites of SAg also were determined; two immunogenic sequences were highly conserved among the species. Many proteins in the National Biomedical Research Foundation database have a sequence similar to that of a uveitopathogenic site. We chemically synthesized many peptides, some of which induced experimental autoimmune uveitis (EAU) and experimental autoimmune pinealitis (EAP) in Lewis rats. In addition, we found native yeast histone H3 capable of inducing EAU. To understand the role in autoimmunity of infectious microorganisms which have cross-reactive antigens, we injected Lewis rats with peptide M, together with one of six different killed bacteria, with or without incomplete Freund's adjuvant (IFA). The rats injected with IFA developed EAU. To assess the impact of infection by live microorganisms, we injected low doses of live Escherichia coli expressing SAg and baker's yeast with a cross-reactive antigen into the rats several times. The rats injected with either live E. coli or live yeast developed EAU. We conclude that infection by microorganisms which have cross-reactive antigens can break immune tolerance to self-antigens and induce inflammatory autoimmune diseases. As an extension of our previous EAU research, we speculated that some types of cataracts may be induced by autoimmune insults. To investigate this issue, we conducted similar experiments: Three groups of four rats were injected three times with lens homogenate, beta-crystallins, or a beta-crystallin (B-A1) emulsified with complete Freund's adjuvant (CFA). All the animals developed severe damage in lens epithelial cells 5 weeks from the date of the first injection. The rats injected with a synthetic peptide derived from Salmonella typhimurium protein, which has five amino acid residues identical to rat beta-crystallin (beta-B2), also induced similar damage. Infection by microbes having antigens homologous to the lens antigens can induce high levels of autoantibodies that provoke lens epithelial cell damage. Thus, autoimmune insult in lens epithelial cells may be an etiology of an initial stage of cataractogenesis. Our future research will focus more on autoimmunity in lens cataractogenesis.